Hepatitis is etiologically classified into viral hepatitis (hepatitis A, B, and C, multiple infection hepatitis, etc.), toxic hepatitis (e.g. drug-induced), and autoimmune hepatitis.
Among them there are hepatitis which frequently follows a subchronic to chronic course (acute hepatitis C) and refractory hepatitis characterized by recurrent episodes of acute exacerbation and ultimate progression to cirrhosis (chronic hepatitis B) . There also is hepatitis which follows a precipitating course, that is fulminant hepatitis.
The treatment of hepatitis includes, in addition to the general therapy for encouraging the mechanism of cure based on rest and diet therapy, antiviral therapy which is instituted for inhibiting growth of the causative virus in cases of viral hepatitis and immunotherapy for potentiating the compromised cellular immunity of the host. The liver drugs available are liver hydrolyzate, glycyrrhizin, reduced glutathione, tiopronin, and polyenephosphatidylchloline, among others. As antiviral aagents, interferons, arabinosyladenine (Ara--A), arabinosyladenosine monophosphate (Ara--AMP), acyclovir, etc. are used. As immunoregulators, glucocorticoids, interleukin-2, picibanil (OK-432), cianidanol, levamisol, etc. are used. Interferons have immunological actions in addition to antiviral activity. Prostaglandin E is known to have a cytoprotective action and is expected to be useful for protection of liver cells. Aside from the foregoing drugs, human epidermal growth factor (hEGF) and human hepatocyte growth factor (hHGF) are known to have cytogenesis promoting activity and their clinical application as liver regeneration promoting factors is considered promising but they are still in the stage of preclinical study.
Recently, vaccine therapy has been recommended for the treatment and prevention of hepatitis B.
However, no satisfactory therapeutic drug for hepatitis is available as yet and there is a standing need for the creation of a drug effective for preventing extensive necrosis and enhancing regeneration of hepatocytes.
It is known that irsogladine maleate (2,4-diamino-6-(2,5-dichlorophenyl)-1,3,5-triazine maleate), which is a benzoguanamine derivative structurally analogous to the compound of the present invention and such that the 2- and 5-positions of phenyl moiety of benzoguanamine have been substituted by chlorine, with both the two amino groups being unsubstituted, has a hepatocyte-protective action and is useful for the treatment of hepatitis (See Japanese Kokai Tokkyo Koho S58-55423, WO 91/01733). Similarly, derivatives also having a 2,5-dichlorophenyl group but having a piperidino or morpholino group in lieu of one of said amino groups, namely 2-amino-4-(2,5-dichlorophenyl)-6-piperidino-1,3,5-triazine and 2-amino-4-(2,5-dichlorophenyl)-6-morpholino-1,3,5-triazine, are known as intermediates for the preparation of antiallergic nicotinoylbenzoguanamine derivatives (Japanese Kokai Tokkyo Koho S57-203083 and S59-104320). Meanwhile, there is a host of known compounds corresponding to benzoguanamine, the phenyl moiety of which is either unsubstituted or halogenated and one of the amino groups of which is substituted. As an example of the compound having an acyclic group substituting one of said amino groups, amino-4-(2-hydroxyethylamino)-6-phenyl-1,3,5-triazine can be mentioned. This compound reportedly is useful as a starting material for production of resins (CA 106:34062). As a compound having a cyclic amino group, 2-amino-4-(4-methylpiperazin-1-yl)-6-phenyl-1,3,5-triazine is known to have an analgesic action (CA 84:135722). However, as to compounds corresponding to benzoguanamine in which both the 2- and 5-positions of its phenyl moiety are substituted by chlorine and one of the amino groups is a substituted amino group, there is no known compound except said compounds substituted by either piperidino or morpholino for one of the amino groups.